Erythromycin

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DRUG INTERACTIONS

Erythromycin use in patients who are receiving high doses of theophylline may
be associated with an increase in serum theophylline levels and potential theophylline
toxicity. In case of theophylline toxicity and/or elevated serum theophylline
levels, the dose of theophylline should be reduced while the patient is receiving
concomitant erythromycin therapy.

Concomitant administration of erythromycin and digoxin has been reported to
result in elevated digoxin serum levels. There have been reports of increased
anticoagulant effects when erythromycin and oral anticoagulants were used concomitantly.
Increased anticoagulation effects due to interactions of erythromycin with oral
anticoagulants may be more pronounced in the elderly.

Erythromycin is a substrate and inhibitor of the 3A isoform subfamily of the
cytochrome p450 enzyme system (CYP3A). Coadministration of erythromycin and
a drug primarily metabolized by CYP3A may be associated with elevations in drug
concentrations that could increase or prolong both the therapeutic and adverse
effects of the concomitant drug. Dosage adjustments may be considered, and when
possible, serum concentrations of drugs primarily metabolized by CYP3A should
be monitored closely in patients concurrently receiving erythromycin.

The following are examples of some clinically significant CYP3A based drug
interactions. Interactions with other drugs metabolized by the CYP3A isoform
are also possible. The following CYP3A based drug interactions have been observed
with erythromycin products in post-marketing experience:

Ergotamine/dihydroergotamine: Concurrent use of erythromycin
and ergotamine or dihydroergotamine has been associated in some patients with
acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.

Triazolobenzodiazepines (such as triazolam and alprazolam) and
related benzodiazepines: Erythromycin has been reported to decrease
the clearance of triazolam and midazolam, and thus, may increase the pharmacologic
effect of these benzodiazepines.

HMG-CoA Reductase Inhibitors: Erythromycin has been reported
to increase concentrations of HMG-CoA reductase inhibitors (e.g., lovastatin
and simvastatin). Rare reports of rhabdomyolysis have been reported in patients
taking these drugs concomitantly.

Sildenafil (Viagra): Erythromycin has been reported to increase
the systemic exposure (AUC) of sildenafil. Reduction of sildenafil dosage should
be considered. (See Viagra package insert.)

There have been spontaneous or published reports of CYP3A based interactions
of erythromycin with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide,
rifabutin, quinidine, methylprednisolone, cilostazol, vinblastine, and bromocriptine.

In addition, there have been reports of interactions of erythromycin with drugs
not thought to be metabolized by CYP3A, including hexobarbital, phenytoin, and
valproate.

Erythromycin has been reported to significantly alter the metabolism of the
nonsedating antihistamines terfenadine and astemizole when taken concomitantly.
Rare cases of serious cardiovascular adverse events, including electrocardiographic
QT/QTc interval prolongation, cardiac arrest, torsades de pointes,
and other ventricular arrhythmias, have been observed. (See CONTRAINDICATIONS.)
In addition, deaths have been reported rarely with concomitant administration
of terfenadine and erythromycin.

There have been post-marketing reports of drug interactions when erythromycin
was coadministered with cisapride, resulting in QT prolongation, cardiac arrhythmias,
ventricular tachycardia, ventricular fibrillation, and torsades de pointes,
most likely due to the inhibition of hepatic metabolism of cisapride by erythromycin.
Fatalities have been reported. (See CONTRAINDICATIONS).